Boron enolates transition state model

Once again, desilylation and oxidative cleavage33 delivers the hydroxycarboxylic acids. A chairlike transition state model, analogous to that proposed for the corresponding boron enolate33, is postulated in order to rationalize the ul topicity of the above titanium enolate. 

Bernard , A., Capelli, A. M., Gennari, C., Goodman, J. M., Paterson, I. Transition-state modeling of the aldol reaction of boron enolates a... 

Under kinetic control, the reactions of prochiral aldehydes with Z-enolates generally lead to syn aldols, while E-enolates lead to anti aldols. The presence of bulky R groups on the enolates, however, may alter these selectivities. The highest diastereoselectivities are observed with boron or titanium enolates. These selectivity trends are interpreted by a concerted cyclic mechanism. The favored transition state resembles a distorted chair, in line with the Zimmermann-Traxler proposals [57, 160, 253] (Figure 6.70). This model has been supported by theoretical studies [9, 40, 41, 125, 1249], Transition states analogous to C2 and C4 (Figure 6.70) are destabilized by 1,3-ecIipsing interactions between the C-R, M-L and C-R bonds, so that models Ci and C3 are more favorable. For the sake of simplification, only the reaction on one face of the enolates is shown in these models, but enolate face selectivity will be discussed later. In some cases, boatlike transition-state models are invoked to interpret selectivity inversions [401, 402, 666], Moreover, Heathcock and coworkers [105] obtained evidence for the influence of an excess of n-B BOTf on the stereoselectivity of the aldol reactions of Z-enolates. In such reactions, anti aldols can be formed preferentially (see bdow). 

Bemardi A, A M Capelli, A Comotti, C Gannari, J M Goodman and I Paterson 1990. Transition-State Modeling of the Aldol Reaction of Boron Enolates A Force Field Approach. Journal of Organic Chemistry 55 3576-3581... 

Chiral boron enolates are effective in enantioselective aldol condensations, a transition-state model being proposed for the moderate chirality transfer exhibited (Scheme 57). ° Diastereoselection with chiral lithium enolates has also been demonstrated by a highly stereoselective synthesis of the Prelog-Djerassi lactonic acid. ... 

Scheme 2.24 Regioselective formation of boron enolates according to Mukaiyama s protocols transition-state model 91 for kinetically controlled enolate generation.

The most widely accepted transition state model of the aldol addition is the Zimmerman-Traxler model [72]. Originally postulated in a seminal paper dating from 1957 for the addition of Ivanov reagents [73] - dianions of phenylacetic acid with MgX as counterions (cf. Section 2.1) - to benzaldehyde, the model postulates a sbc-membered chair-like transition state. This hypothesis was adapted to a numerous aldol additions performed with a large variety of enolates of hthium, boron, and other metals. The strength of this model is a convincing explanation for the cis-syn, trans-anti correlation, as outlined in Scheme 4.30. 

Scheme 4.46 Evans-syn" selective aldol addition of valine-derived N-propionyl oxazolidinone 48 via boron enolate 208. Dipole-minimized transition state model 210.

Scheme 4.62 Stereodivergence in aldol additions of Oppolzer s sultam 92 via boron, tin, and silicon enolates. Proposed transition state models 273-275.

Bemardi A, Capelli AM, Comotti A, Gennari C, Gardner M, Goodman JM, Paterson I. Origins of stereoselectivity in chiral boron enolate aldol reactions a computational study using transition state modellings. Tetrahedron 1991 47 3471-3484. 

Aldol and related reactions may also be chelation-controlled. Boron enolates of N-acyloxazolidinones 19 are chelated in the ground state. Their reactions with aldehydes will necessitate the coordination of the aldehyde with the boron atom at transition state, so that the initial bidentate chelate will be broken (Figure 1.26). However, the titanium atom of related titanium enolates can accommodate hexa-coordination so that the initial titanium chelate 20 does not need to be disrupted. In each case, the aldol reaction leads to different syn stereoisomers (Figure L26) via transition models 21 and 22. 

Figure 4. Prediction of stereochemistry of boron enolates 9 and 10 using chair-type six-membered transition state based on the Zimmerman model.

A similar model has been applied to aldol condensation reactions of boron enolates. O The reaction of E) enolate 369, for example, can lead to either transition state 371 or 372. Transition state 371 generates the... 

For the enolates of alkali metals and magnesium, their known tendency for aggregation was put forward against the Zimmerman-Traxler model that assumes monomeric enolates as the reactive species. However, even the aggregation is compatible with the model if one assumes a sbc-membered transition state to operate at tetrameric lithium enolates, as postulated by Seebach and coworkers [74]. The fact that a more precise cis-sy -correlation is observed for enolates of boron, titanium, or tin is also compatible with the Zimmerman—Traxler model. For these stronger Lewis acids (compared to alkali metals or magnesium), the six-membered transition state will be tighter, so that steric effects become more important. 

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